Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone.

Testosterone therapy (TTh) in hypogonadal men was associated with a statistically significant reduction in all-cause mortality risk compared to untreated or placebo controls.

• Pooled hazard ratio for overall mortality was HR: 0.70 (95% CI: 0.54–0.90; P < .01)
• The meta-analysis included 10 studies involving 179,631 hypogonadal men
• The analysis used weighted time-related measures of risk (hazard ratios) across all included studies
• The study was registered on PROSPERO (CRD42022301592) and performed according to MOOSE and PRISMA guidelines

Testosterone therapy in hypogonadal men was not associated with an increased risk of cardiovascular events compared to untreated or placebo controls.

• Pooled hazard ratio for cardiovascular events of any type was HR: 0.98 (95% CI: 0.73–1.33; P = .89)
• The result was not statistically significant, indicating no unfavorable cardiovascular effect of TTh
• Cardiovascular events included events of any type as defined by the individual included studies
• The 10 included studies had high heterogeneity in terms of population, hypogonadism definition, type of TTh, cardiovascular event definition, and length of follow-up

The meta-analysis included 10 comparative studies involving 179,631 hypogonadal men with treatment and control arms.

• Included studies required male adults aged ≥18 years diagnosed with hypogonadism divided into a treatment arm (any TTh) and a control arm (observation or placebo)
• Single-arm, non-comparative studies were excluded, as were studies not reporting hazard ratios for the chosen outcomes
• Studies were required to assess the risk of death and/or cardiovascular events
• The systematic review followed MOOSE and PRISMA guidelines

High heterogeneity among included studies was identified as a main limitation of the meta-analysis.

• Heterogeneity was noted across multiple dimensions: included population, definition of hypogonadism, type of TTh used, definition of cardiovascular event, and length of follow-up
• The authors identified an urgent need for collecting long-term follow-up data
• The analysis was restricted to time-related measures of risk (hazard ratios) only

The authors concluded that untreated hypogonadal men face increased risk of long-term morbidity and early mortality, underscoring the clinical importance and safety of TTh in true hypogonadal men.

• The conclusion was based on time-related measures of risk only
• The authors described an 'increased risk of long-term morbidity and early mortality for untreated hypogonadal men'
• TTh was described as potentially playing 'a role in reducing the overall risk of death without increasing cardiovascular events risk'
• The authors emphasized the 'clinical importance and safety of TTh in true hypogonadal men'